Genomic Profiling of Saudi patients with Colorectal Cancer using Next Generation Sequencing


Session type:


Saleh Alghamdi1,Alhanouf Alomani2,Bader Almuzaini2,Abdullah Alsharm1,Fida Aljaser3



Colorectal cancer (CRC) is a complex malignant tumour with diverse molecular changes. The advancement in the understanding of genetic mutations underlying the pathogenesis of colorectal cancer are the mainstay of developing diagnostic, prognostic, and even therapeutic approaches according to the molecular profile of each individual. particularly, when such mutational hotspots Correlated with various demographical and Clinicopathological features.


Targeted next generation sequencing of 58 formalin-fixed paraffin-embedded tissues (FFPE) from patients with colorectal adenocarcinomas was performed using the Comprehensive Cancer Panel on the Ion Torrent™ platform. Chart reviews were done to collect the demographic and clinicopathological features from the hospital information system. Correlation of the identified variants on 12 cancer susceptible genes, KRAS, NRAS, BRAF, APC, PIK3CA, PTEN, SMAD4, TP53, MSH2, MSH6, MLH1 and PMS2 with demographical and Clinicopathological features of the patients was performed using Fisher’s exact test.


Our primary data reveal the common variations which known to be correlated with colorectal cancer in different stages and tumour sites. In total of 58 samples, around 15014 genetic variants were identified in 535 genes. 79 somatic variants were detected in 87.9% (51/58) of CRC patients affecting 10 genes after applying a specific filter to sort out genetic variation in only 12 common genes associated with colorectal cancer. Of these variants, KRAS (86.2%) was the most frequent mutated gene, followed by APC (81%), TP53 (48.2%), MSH6 (20.6%), BRAF (20.6%), MSH2 (18.9%), MLH1 (17.2%), SMAD4 (17.2%), and PIK3CA (17.2%). The least frequent mutated gene was NRAS (1.7%). Overall, there were 47 pathogenic variants identified in our study and previously reported in the COSMIC database. Among all pathogenic variants, 36 (76.6%) were reported to be related to large intestine cancers whereas the remaining eleven variants were reported with other cancers.


The top three genes (i.e. KRAS, APC, TP53) with the highest mutation frequency in our cohort were the same as reported in COSMIC. However, the differences in their ranking order (APC, TP53, KRAS; in COSMIC) suggests possible population effects. This shows the importance of targeted NGS as a key tool to elucidate different molecular markers which could be used as diagnostic/prognostic marker for colorectal cancer.